Endometrial hyperplasia (EH), a pre-cancerous condition of excessive proliferation of the endometrium, generally arises in the context of chronic estrogen exposure unopposed by progesterone. It represents a continuum of histologically distinct processes, starting from simple EH without atypia that progresses to complex EH without atypia, followed by complex EH with atypia. The presence of the most severe form of EH (complex EH with atypia) in an endometrial biopsy denotes a high (29%-52%) risk of concurrent and future endometrial cancer (EC). Current treatment approaches for EH are limited, involving primarily hysterectomy or hormone therapy. Growing evidence has shown progressive increases in cyclin D1 expression in human endometrial glands with complex hyperplasia and in endometrioid adenocarcinoma, compared with healthy human endometrium tissue. SHetA2 is a nontoxic, orally bioavailable drug that causes cyclin D1 degradation and G1 cell cycle arrest in transformed cells. SHetA2 also induces decreases in cyclin D1 in uterine tissues from mice treated with oral or vaginal suppository administration, compared with control mice. Furthermore, SHetA2 selectively triggers apoptosis in tumor cells by inhibiting migration of the chaperone GRP75 and its client proteins (such as the ER) to the mitochondria. The purpose of this Task Order is to evaluate the effects of oral and vaginal forms of SHetA2 on the development of EH and EC in a rodent model.